This invention relates to the preparation of L-aspartic acid N-thiocarboxyanhydride, which is a useful intermediate for the synthesis of peptides. In particular, L-aspartic acid N-thiocarboxyanhydride is useful for reaction with L-phenylalanine lower alkyl esters to form L-aspartyl-L-phenylalanine lower alkyl esters, which are useful as potent sweetening agents for use in foodstuffs and beverages. The methyl ester is especially preferred as a sweetening agent.
The preparation of amino acid N-thiocarboxyanhydride derivatives is described in J. Org. Chem. 36, 49 (1971). One method described therein is the reaction of an amino acid with carbonyl sulfide in an alkali metal hydroxide solution, to form an alkali metal salt of the amino acid thiocarbamate, which is then reacted with a phosphorus trihalide to provide a mixture of the N-thiocarboxyanhydride and the N-carboxyanhydride. However, in efforts to apply this method to the preparation of L-aspartic acid N-thiocarboxyanhydride, only low yields of product have been obtained.